Impact of gamma irradiation and ethylene oxide sterilisation on the stability of crystalline and amorphous drug solids

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dc.contributor.authorElkhashab, Mohamed
dc.contributor.authorSartawi, Ziad
dc.contributor.authorLynch, Denis
dc.contributor.authorVucen, Sonja
dc.contributor.authorCrean, Abina
dc.contributor.funderTaighde Éireann – Research Ireland, 12/RC/2275(P2)
dc.date.accessioned2026-10-20T14:37:02Z
dc.date.available2026-10-20T14:37:02Z
dc.date.issued2026-06-20
dc.description.abstractTerminal sterilisation is a critical process for pharmaceutical products intended for parenteral or invasive administration, yet conventional sterilisation approaches can compromise thermolabile or chemically sensitive drug substances. In this study, the compatibility of crystalline and amorphous solid forms of five drug substances (betamethasone dipropionate (BMD), estradiol (E2), itraconazole (ITZ), vismodegib (VDG), and zolmitriptan (ZMT)) with sterilising gamma irradiation and ethylene oxide (EtO) cycles was evaluated in terms of chemical and physical stability. Physical stability was assessed by visual inspection of crystalline powders and amorphous solids pre- and post-sterilisation and by differential scanning calorimetry (DSC) to characterise the melting behaviour of crystalline drugs, and glass transition and recrystallisation events in amorphous forms. Chemical stability was examined using reverse phase-high-performance liquid chromatography (RP-HPLC), liquid chromatography–mass spectrometry (LC-MS), and proton nuclear magnetic resonance spectroscopy (¹H-NMR).Gamma irradiation and EtO preserved the chemical integrity of BMD, E2, ITZ, and VDG. A reversible colour change observed for ITZ was attributed to radical formation as confirmed by gentle heating, HPLC and LC-MS. E2 demonstrated alterations in crystallinity and thermal behaviour after sterilisation, despite maintaining chemical integrity. ZMT exhibited pronounced sensitivity to sterilisation: gamma irradiation induced physical softening and oxidative degradation, particularly in the amorphous form, while EtO sterilisation induced ZMT hydroxyethylation, as confirmed by LC-MS identification of multiple alkylated derivatives.Overall, sterilisation compatibility was governed primarily by molecular structure rather than the drug solid-state. These findings provide an insight for selecting sterilisation strategies and facilitate the translation of crystalline and amorphous pharmaceutical solids toward clinical application.en
dc.description.sponsorshipTaighde Éireann – Research Ireland|12/RC/2275(P2)
dc.description.versionPublished Version
dc.format.extent12
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid107572
dc.identifier.authororcidElkhashab, Mohamed
dc.identifier.authororcidSartawi, Ziad
dc.identifier.authororcidLynch, Denis
dc.identifier.authororcidVucen, Sonja§0000-0003-0140-0121
dc.identifier.authororcidCrean, Abina§0000-0001-6171-0303
dc.identifier.citationElkhashab, M, Sartawi, Z, Lynch, D, Vucen, S & Crean, A 2026, 'Impact of gamma irradiation and ethylene oxide sterilisation on the stability of crystalline and amorphous drug solids', European Journal of Pharmaceutical Sciences, vol. 224, 107572, pp. 1-12. https://doi.org/10.1016/j.ejps.2026.107572
dc.identifier.doi10.1016/j.ejps.2026.107572
dc.identifier.endpage12
dc.identifier.issn0928-0987
dc.identifier.journaltitleEuropean Journal of Pharmaceutical Sciences
dc.identifier.otherORCID: /0000-0003-0140-0121/work/230766561
dc.identifier.otherORCID: /0000-0001-6171-0303/work/230767054
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/19464
dc.identifier.volume224
dc.language.isoen
dc.publisherElsevier B.V.
dc.relation.urihttps://www.scopus.com/pages/publications/105042227811
dc.rights© 2026, authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.statusPeer reviewed
dc.subjectEthylene oxide
dc.subjectGamma irradiation
dc.subjectPhysicochemical stability
dc.subjectSolid-state characterisation
dc.subjectTerminal sterilisation
dc.subject[Chemistry]
dc.subject[Pharmacy]
dc.titleImpact of gamma irradiation and ethylene oxide sterilisation on the stability of crystalline and amorphous drug solidsen
dc.typeArticle (peer-reviewed)
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